Uridine 3-deoxy

Fig. 14.1 Cellular pathway of methotrexate. ABCBl, ABCCl-4, ABC transporters ADA, adenosine deaminase ADP, adenosine diphosphate AICAR, aminoimidazole carboxamide ribonucleotide AMP, adenosine monophosphate ATIC, AICAR transformylase ATP, adenosine triphosphate SjlO-CH -THF, 5,10-methylene tetrahydrofolate 5-CHj-THF, 5-methyl tetrahydro-folate DHFR, dihydrofolate reductase dTMP, deoxythymidine monophosphate dUMP, deoxy-uridine monophosphate FAICAR, 10-formyl AICAR FH, dihydrofolate FPGS, folylpolyglutamyl synthase GGH, y-glutamyl hydrolase IMP, inosine monophosphate MTHFR, methylene tetrahydrofolate reductase MTR, methyl tetrahydrofolate reductase MTX-PG, methotrexate polyglutamate RFCl, reduced folate carrier 1 TYMS, thymidylate synthase. Italicized genes have been targets of pharmacogenetic analyses in studies published so far. (Reproduced from ref. 73 by permission of John Wiley and Sons Inc.)...

The use of radi olabeled nucleic acid precursors, primarily tritiated thymidine or (deoxy)uridine, however, is subject to numerous drawbacks. Nevertheless, the use of radiolabeled precursors have provided some promising clinical correlation data [174]. 

This interesting methodology broadens the preceding electron transfer reduction of acetates and pivaloates, and seems very efficient for synthesizing protected 2 -deoxy uridine such as 85 in high yields (85 %) (Scheme 44). 

The spectra of the neutral species (pH 1-7) of uridine87 (see Fig. 6), 2-deoxy-uridine,44 87 thymidine (see Fig. 7),87 and l-jS-D-ribofuranosylthymine88 (see Fig. 8) resemble those for the neutral species of uracil, 1-methyluracil, and 3-methyluracil, and, on this basis, it would be impossible to assign the position of the carbohydrate... 

Arylhalide 5 -iodo-2 -deoxy- uridine monophosphate Thymidine kinase Both iodine and nucleotide covalently incorporated. Only nucleotide incorporation parallels inhibition of enzyme activity (Chen et al., 1976). 

SYNS DEOXYFLUOROURIDINE l-p-d-2 -DEOXYRIBOFURANOSYL-5-FLUOROURACIL FDUR FLOXURIDIN FLOXURIDINE FLUORODEOXY-URIDINE p-5-FLUORO-2 -DEOXYURIDINE 5-FLUORODEOXYURIDINE 5-FLUORO-2-DEOXY-URIDINE 5-FLUORO-2 -DEOXYURIDINE 5-FLUOROURACIL DEOXYRIBOSIDE 5-FLUORO-URACIL-2 -DE0XYRIB0SIDE FLUORURIDINE DEOXYRIBOSE FUDR 5-FUDR NSC-27640 RO 5-0360... 

In nucleotides, azides have been used for the introduction of amino groups into either the purine moiety, as in the synthesis of 8-aminoadenosine , or into the sugar moiety, as in the synthesis of 5-amino-5-deoxy uridine . 

Bro mo-2 -deoxy uridine / -6-Azauridine [106a]/ (0-D-Arabinofuranosyl)-6-azauracil... 

Kawaguchi, T. et al. Control of drug release with a combination of prodrug and polymer matrix antitumor activity and release profiles of 2 ,3 -Diacyl-5-fluoro-2 -deoxy-uridine from poly(3-hydroxybutyrate) microspheres. J. Pharmaceutical Sci. 1992, 87(6), 508-512. 

Nucleosides prepared conventionally from deoxy-sugars have included the antiviral nucleoside dihydro-5-azathymidine (12), the tritiated analogue (13), and the 6-substituted derivatives (14) (Scheme 2), [ C-2] and [ C-4]-2-deoxy-uridine, and 2-deoxy-ribonucleosides from 5-azapyrimidine derivatives, ... 

Routine syntheses of nucleotides have not been covered. Syntheses of more unusual derivatives have included adenosine and uridine 5 -(1-amino)ethylphos-phonate, which are unaffected by alkaline phosphatase, and 5-fluoro-2 -deoxy-uridine 5 V-azidophenylphosphate, used as a photo-affinity label for thymidylate synthetase. 

A further report on the reactions of 5-azido-5-deoxy uridine (see Vol. 12, p. 166) describes its cyclization in presence of DDQ to give the bridged compounds (68) or (69). ... 

Dicarboxylic acid 5 -monoesters of thymidine and of 5-(2-thienyl)-2 -deoxy-uridine have been prepared as triphosphate mimics. The ester of d4T with citric acid has also been made with the same objective, and more lipophilic bioisosteres 237 and the AZT equivalent have been reported, these being designed to mimic the conformation of the nucleoside triphosphate when complexed to a metal ion. Neither of these last two classes were effective, since all the activity against HIV could be shown to be due to hydrolysis to the parent nucleoside. 

Raman spectra of nine crystals containing guanosine moieties have been reported useful correlations were obtained with the conformations previously established by X-ray studies.The temperature-dependent CD spectra of a- and P-5-substituted-2 -deoxy-uridines indicate an increase in the proportion of syn isomer in changing from aqueous to ethanolic solution. > 68 preferred... 

Deoxy uridine triphosphate (dUTP) and biotin-16-deoxy uridine triphosphate (Biotin-16-dUTP) (Boehringer Mannheim). 

Br]-2 -Bromo-2-deoxy-uridine has been prepared either from 2,2 -anhydro-uridine using radio labelled ammonium bromide or by irradiation of unlabelled... 

K. Ganeshaguru and A.V. Hoffbrand. The effect of deoxy-uridine, vitamin B12, folate and alcohol on the uptake of thymidine and on the deoxynucleoside triphosphate concentrations in normal and megaloblastic cells. Brit. J. Haematol. 40 29, 1978. 

---